有机溶剂的特性精.ppt

有机溶有机溶剂的特性精的特性精有機溶劑的特性v溶解性溶解性脂溶性（可溶解脂肪）愈強，去脂效能愈佳，對皮脂溶性（可溶解脂肪）愈強，去脂效能愈佳，對皮膚和神經系統的傷害也愈大膚和神經系統的傷害也愈大v可燃性可燃性可燃性高者作燃料，不可燃者則作滅火劑。可燃性高者作燃料，不可燃者則作滅火劑。v揮發性揮發性蒸氣壓愈高，揮發性愈強，空氣中有機溶劑的濃度蒸氣壓愈高，揮發性愈強，空氣中有機溶劑的濃度愈大，愈多經由呼吸道吸入人體。愈大，愈多經由呼吸道吸入人體。v化學結構化學結構一般而言，結構相似者毒性可能相近，例如鹵化有一般而言，結構相似者毒性可能相近，例如鹵化有機溶劑（四氯甲烷，三氯乙烯，四氯乙烯等），對機溶劑（四氯甲烷，三氯乙烯，四氯乙烯等），對肝皆具毒性。也可能差很多，肝皆具毒性。也可能差很多，2,4-diaminotoluene(liver tumor)/2,6-diaminotoluene(not)Themaindeterminantsofasolventsinherenttoxicity thenumberofcarbonatomlipophilicityvolatilitywhetheritissaturatedorhasdoubleortriplebondsbetweenadjacentcarbonatomsitsconfiguration(straightchain,branchchain,orcyclic)thepresenceoffunctionalgroupsex.Amides/amines-potentsensitizeraldehyde-irritatingRoute of ExposurevPrimary routeRespiratorylRelated to volatility of solventlLipid solubilitylMACvSecondary routeSkinIngestion(accident)Sources of exposure vDaily activity-workplace,gas station,smoking,household,etc.vSolvent abuse-produce euphoria,delusions,sedation and visual and auditory hallucinationvEnvironmental contamination major volatile organic solvents(VOCs)Occupational Standards:TWAThe time-weighted average is the time-weighted average concentration for a normal 8-hour workday or 40-hour workweek,to which nearly all workers may be repeatedly exposed,day after day,without adverse effect.As shown in the figure,time weighted averages permit excursions above the limit provided that they are compensated by equivalent excursions below the limit during the workweekTWATWAToillustratetheTWAformula,assumethatasubstancehasan8-hourtime-weightedaveragePELof100ppm.Assumethatanemployeeissubjecttothefollowingexposure:Twohoursexposureat150ppmTwohoursexposureat75ppmFourhoursexposureat50ppm.Substitutingthisinformationintheformula,wehave:TWA=(150)(2)+(75)(2)+(50)(4)=81.25ppm8Since81.25ppmislessthan100ppm,the8-hourtime-weightedaveragelimit,theexposureisacceptableShort-TermExposureLimit(TLV-STEL)the maximum concentration to which workers can be exposed continuously for a short period of time(15-minute)without suffering from irritation,chronic or irreversible tissue change,or narcosis of sufficient degree to increase accident proneness,impair self-rescue,or materially reduce work efficiency.Ceiling(TLV-C)vCeiling(TLV-C)istheconcentrationthatshouldnotbeexceededeveninstantaneously.vForsomesubstances,forexampleirritantgases,onlytheTLV-ceilingmayberelevant.General AcuteToxic EffectsvCNSdepression-High level exposure-中樞神經麻醉效果，例如乙醚麻醉 一般而言，碳鏈愈長，含雙鍵、鹵素基（氯、溴、氟等）的溶劑中樞效果愈強。臨床上，暴露的人會頭暈、頭痛、噁心、嘔吐、嗜睡，平衡失調，像醉酒一般，除了影響健康外，勞工甚易發生工作意外。工作場所中常存在多種溶劑或混合物，彼此加強作用，危害比單一物質更大。-Subanesthetic dosebehavioral toxicityvDermalandmucousirritationSolvent-induced chronic encephalopathy(CSE)vNonspecificsymptoms(headache,fatigue,sleepdisorders)withorwithoutchangesinneuropsychologicaldysfunctionvTypeISymptomsonlyvType 2A Sustained personality or moodchangevType 2B Impairment in intellectualfunctionvType3Dementia刺激性或過敏性皮膚炎v有有機機溶溶劑劑具具去去脂脂性性，能能溶溶解解皮皮膚膚表表面面油油脂脂，引引起起皮皮膚膚炎炎。暴暴露露濃濃度度愈愈高高，時時間間愈愈長長，或或溶溶劑劑封封閉閉在在手手套套內內無無法法揮揮發發，造造成成的的傷傷害害愈愈大大。在在工工廠廠內內有有一一個個動動作作十十分分容容易易傷傷害害皮皮膚膚，即即是是用用溶溶劑劑來來洗洗手手，去去除除污污垢垢。殊殊不不知知長長期期下下來來，油油脂脂儘儘失失，往往往往引引起起刺刺激激性性或或過過敏敏性性皮皮膚膚炎炎。皮皮膚膚炎炎的的臨臨床床表表現現分分急急慢慢性性兩兩種種，急急性性呈呈紅紅，腫，慢性呈乾，裂的濕疹樣變化。腫，慢性呈乾，裂的濕疹樣變化。Biomarkers of solventsvMeasurements of blood or urine levels of chemicals following exposure(not highly specific)vCharacterization and quantitation of unique metabolites in body fluidsvMeasurement of covalent binding of reactive metabolites to proteins,lipids,or nucleic acidsvChemically related and specific forms of chromosome damageMetabolismvMetabolicinactivation(detoxification)toluenevMetabolicactivation(bioactivation)benzeneP450isozymesexhibitspecies-,substrate-,andregion-selectivityCYP 2E1(1)v2E1 active in both hepatic and non-hepatic tissuesvsubstrate preference-mainly for simple aliphatic compounds(solvents)oxidizes small straight-chain or branched-chain compounds(no rings)lalcohols(methanol,ethanol),acetone and ketone bodies,short-chain fatty acidslchlorinated solvents-chloroform,trichloroethylene(TCE),carbon tetrachloride,etc.oxidizes benzene(single unsubstituted aromatic ring)CYP 2E1(2)vBioactivationaliphatic epoxides and aldehydes are reactive metabolites(liver damage)benzene epoxide(myelotoxicity)-bone marrow cell damage-leukemiavslightly inducible by small aliphatic compounds/also prolongs enzyme activityEtOH-inducible P450(ethanol)-2-5 x increase CYP 2E1 levelsMetabolitesvGenerationofbiologicreactiveintermediatesa.Inactivated by glutathione,ascorbic acid and other cellular antioxidantsb.covalent bind to cellular macromolecules inactivation of receptors and specific proteins,damage to cell membranes,or initiation of mutagenic reactions c.Metabolic saturation-detoxication pathwaybioactivation pathwayvGeneration of reactive oxygen species-freeradical,ROSP450 inducers and inhibitorsvInducers-ethanol,acetone,ketones,PAH,certain drugs(phenobarbital,phenytoin,diazepam,rifampicin),smokingvInhibitors-disulfiram,3-amino-1,2,4-triazole,several constituents of foods(diallyl sulfide,dihydrocapsaicin,phenylethyl isothio cyanate)vSuicideinhibitors1,2-dichloroethylenevs.CYP2E1Alkanes and AlkenesvCarbonchainsSimplelStraight or branchedvGenerallyhighlyvolatileandlipophilicvExamplesPentane,hexane,octanePaint thinners,enamels,varnishesAlkanes and AlkenesvSolubilizeoremulsifyfatsvRespiratoryEffectsIrritation/swelling of mucous membranesBronchoconstrictionPulmonary edemavCNSAnesthesia and narcosisvSkinIrritation and swellingHalogenated HydrocarbonsGeneralStructure H of hydrocarbon replaced by F,Cl,Br,INames Halogen named as substituent groupF fluoro Cl-chloroBr-bromo I-iodo Examples:dichloromethane=CH2Cl2 1,2-dibromoethane=CH2Br-CH2BrHalogenated HydrocarbonsChloroform,dichloromethane,carbon tetrachlorideHeptatoxicity-fatty liver and necrosisnumbers of halogens,size,ease of homolytic cleavagetoxicityDichloromethane(methylene chloride)Solvent for removing paint or degreasingRemoval of caffeine from coffeeToxic effectslCNS depressionlMetabolized to CO hypoxiaChloroformvEarliestanestheticsvAcuteeffectsAnesthesia,cardiac arrhythmiasvChroniceffectsLiver damagelMetabolism to reactive metabolitePhosgene Centrilobular necrosis,fatty liverKidney damageCarbon TetrachloridevUsesSolvent,cleaning agent,fire extinguisherAntihelminthic for humansvExposureOccupationalFound in groundwater and waste sitesCarbon TetrachloridevToxicityHepatotoxiclForms reactive metaboliteslCentrilobular necrosis,fatty liver2E1Inhibit microsomal ATPase activity within minutesSingle cell necrosis 5-6 hr Maximal centrolobular necrosis 24-48 hCYP2E1 inhibitors can prevent CCl4 toxicityTCE has multiple effects:Several forms of cancer.neurotoxicity,immunotoxicity,developmental toxicity,liver toxicity,kidney toxicity,and endocrine effects.TCE acts through multiple metabolites and metabolic pathways:CYP450 metabolites include TCA,DCA.GST metabolites include DCVC.TCE acts through multiple modes of action.Trichloroethylene(TCE)Kidney tumorsDCVC is bioactivated in proximal tubular cells to reactive thiolS-(1,2-dichlorovinyl)thiolLiver tumorsExpression of CYP2E1 in the hepatocytesTCA and DCALung cancerChloral hydrate accumulation in Clara cellsTetrachloroethylenevwidelyusedfordry-cleaningfabricsandmetaldegreasingoperationsvliver,kidney,andcentralnervoussystem(CNS)fromacuteandchronicinhalationexposuretotetrachloroethylenevprobablycarcinogenictohumansAlcoholsvEthylalcoholSolvent,intoxicating beverageOccupational exposure minorToxic effectslCNS depressionDisrupt cell membraneBlock NMDA receptorslFetal alcohol syndromelHepatotoxicMetabolism to acetaldehydeROSMalnutritionPossible mechanisms of alcoholvmembranefluiditydisplacementofmembrane enzyme and alteration thefunctionofmembrane,thereticularactivatingsystemismostsensitivevblocktheNMDAreceptorvinterferewithATP-gatedionchannelMethanolSolventIndustrial exposureToxicitylPermanent blindnessDamages retina and optic nervelMetabolized to formic acidAccumulates in tissues COCO2 2+H+H2 2OOFormicacidFormaldehydeMethanolTetrahydrofolateAlcohol dehydrogenaseAldehyde dehydrogenaseMethanol intoxicationvNeurologicsymptoms:headache dizzinessamnesiarestlessnessacute manialethargyconfusioncomaconvulsionsOPHTHALMOLOGIC TOXICITYvTarget-retina-optic disk and optic nervevOccur when serum pH drops below 7.2vLow pH intracellular concentration of formatevImprovement of vision with correction of acidosis,because formate moves out of the cellvFormate is an inhibitor of cytochrome oxidase,which could inhibit ATP formation in the optic nerveTreatment EthanoltherapyHemodialysiseffectivelyremovesmethanolanditstoxicmetabolites4-methylpyrazole(4-MP)“Fomepizole”:amorepotentinhibitorofalcoholdehyrogenaseFolatetherapySodiumbicarbonateEthylene GlycolvUsesHeat exchangers,antifreeze,hydraulic fluid,industrial solventsvExposureVapor or mistGroundwaterAccidentalvTreatmentthesameasmethanolAromatic HydrocarbonsvBenzene,tolueneandxylenevMostcommonaromatichydrocarbonsfoundinpetroleumvHighvolatilityvLowwatersolubilityvPrioritypollutantsBenzenevUsesPetroleum industryStarting material in chemical synthesisvExposurePrimarily workplace lInhalation of benzene vaporslSkin absorptionBenzene ToxicityvMechanism(Chronic)Conversion of benzene to reactive metabolitelBenzene oxide Quinones,semiquinoneslInitial reactions LiverlFinal reactions Bone marrowCovalently bind to DNA,RNA and proteinsROSToluene and XylenevUsesSynthesis of resins,plastics,gasoline additivesPaints,thinners,glues,cleaning agentsvExposureLow levelIndustrial workers,gas station attendantsvToluenemorelipophilicthanbenzeneToluene and Xylene ToxicityvAcuteCentral nervous systemlDepression,narcosisGastrointestinal disturbancesvChronicImpaired cognition,reaction timesHearing lossPossible mechanism of CNS effects of toluene Change membrane fluidity altering intracellular communicationPartition into hydrophobic regions of proteins altering membrane bound enzyme activity and/or receptor activityNeurotransmitterEnhance GABAA receptorAttenuate NMDA receptor,nicotinic receptorActivate dopamine systemsPolycyclic Aromatic Hydrocarbons(PAHs)vTwoormorefusedaromaticringsvLargegroupofchemicalsvPrioritypollutantsvSourcesIncomplete combustion of organic materiallAutomobiles,manufacturingPAHsvTransportReleased into atmospherelMovementDepositionlSurface waterlPlantslSedimentslGround waterPAHsvExposureWidely distributed in environmentSurface waterlDeposition of airborne PAHslWastewater discharge,storm water runofflIndustrial dischargesFoodlGrilled/smoked meatslLeafy vegetables and grainsTobacco smokePAHsvExposureInhalationOralSkinvStoredinkidneyandlivervLipophilicResistant to degradation in environmentvToxicityReactive metabolitesPotential carcinogensHEALTH EFFECTSvInadditiontoskincancervReportsindicatinghigherincidencesof:Respiratory tract tumorsUpper gastrointestinal tract tumors vDuetooccupationalexposureofPAHs谢谢！